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. 1999 Mar;79(7-8):1255–1261. doi: 10.1038/sj.bjc.6690201

Prognostic value of p53 protein expression for patients with gastric cancer – a multivariate analysis

Y Maehara 1, M Tomoda 1, S Hasuda 1, A Kabashima 1, E Tokunaga 1, Y Kakeji 1, K Sugimachi 1
PMCID: PMC2362221  PMID: 10098768

Abstract

Mutations in the p53 gene, one of the most common genetic alterations in human cancer, are implicated in tumorigenesis and tumour progression. Although p53 protein expression appears to be correlated to prognosis in patients with malignancy, its prognostic role in gastric cancer has remained controversial. We examined the clinical significance of p53 overexpression in 427 patients with gastric cancer, using multivariate analysis. Tumour sections of gastric cancer tissues from these 427 Japanese patients were stained immunohistochemically with monoclonal antibody PAb1801. The presence of p53 expression was statistically compared with clinicopathological features and post-operative survival, using univariate and multivariate analyses. p53 expression was detected in 38.6% (165 out of 427) of these gastric cancers and immunoreactivity was not observed in normal mucosa adjacent to the tumour. A higher rate of p53 detection was observed among large tumours and in those with a prominent depth of invasion, lymphatic and vascular invasion and lymph node involvement. Prognosis was significantly worse for patients with p53-positive-staining tumours. The 5-year survival rate was 62.5% for patients with p53-negative tumours and 43.3% for those with positive malignancies. p53 expression was a significant prognostic factor for node-positive gastric cancers in subjects undergoing treatment with curative resection, as assessed by Cox regression analysis. Thus, the expression of p53 was closely related to the potential for tumour advance and a poorer post-operative prognosis for patients with gastric cancer. © 1999 Cancer Research Campaign

Keywords: gastric cancer, p53 expression, prognosis, multivariate analysis

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Selected References

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  1. Allred D. C., Clark G. M., Elledge R., Fuqua S. A., Brown R. W., Chamness G. C., Osborne C. K., McGuire W. L. Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. J Natl Cancer Inst. 1993 Feb 3;85(3):200–206. doi: 10.1093/jnci/85.3.200. [DOI] [PubMed] [Google Scholar]
  2. Banks L., Matlashewski G., Crawford L. Isolation of human-p53-specific monoclonal antibodies and their use in the studies of human p53 expression. Eur J Biochem. 1986 Sep 15;159(3):529–534. doi: 10.1111/j.1432-1033.1986.tb09919.x. [DOI] [PubMed] [Google Scholar]
  3. Bozzetti F., Bonfanti G., Bufalino R., Menotti V., Persano S., Andreola S., Doci R., Gennari L. Adequacy of margins of resection in gastrectomy for cancer. Ann Surg. 1982 Dec;196(6):685–690. doi: 10.1097/00000658-198212001-00012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brambilla E., Gazzeri S., Moro D., Caron de Fromentel C., Gouyer V., Jacrot M., Brambilla C. Immunohistochemical study of p53 in human lung carcinomas. Am J Pathol. 1993 Jul;143(1):199–210. [PMC free article] [PubMed] [Google Scholar]
  5. Carson D. A., Lois A. Cancer progression and p53. Lancet. 1995 Oct 14;346(8981):1009–1011. doi: 10.1016/s0140-6736(95)91693-8. [DOI] [PubMed] [Google Scholar]
  6. Chang F., Syrjänen S., Syrjänen K. Implications of the p53 tumor-suppressor gene in clinical oncology. J Clin Oncol. 1995 Apr;13(4):1009–1022. doi: 10.1200/JCO.1995.13.4.1009. [DOI] [PubMed] [Google Scholar]
  7. Chin K. V., Ueda K., Pastan I., Gottesman M. M. Modulation of activity of the promoter of the human MDR1 gene by Ras and p53. Science. 1992 Jan 24;255(5043):459–462. doi: 10.1126/science.1346476. [DOI] [PubMed] [Google Scholar]
  8. Cross S. M., Sanchez C. A., Morgan C. A., Schimke M. K., Ramel S., Idzerda R. L., Raskind W. H., Reid B. J. A p53-dependent mouse spindle checkpoint. Science. 1995 Mar 3;267(5202):1353–1356. doi: 10.1126/science.7871434. [DOI] [PubMed] [Google Scholar]
  9. Elledge R. M., Gray R., Mansour E., Yu Y., Clark G. M., Ravdin P., Osborne C. K., Gilchrist K., Davidson N. E., Robert N. Accumulation of p53 protein as a possible predictor of response to adjuvant combination chemotherapy with cyclophosphamide, methotrexate, fluorouracil, and prednisone for breast cancer. J Natl Cancer Inst. 1995 Aug 16;87(16):1254–1256. doi: 10.1093/jnci/87.16.1254. [DOI] [PubMed] [Google Scholar]
  10. Finlay C. A., Hinds P. W., Tan T. H., Eliyahu D., Oren M., Levine A. J. Activating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half-life. Mol Cell Biol. 1988 Feb;8(2):531–539. doi: 10.1128/mcb.8.2.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Furihata M., Ohtsuki Y., Sonobe H., Shuin T., Yamamoto A., Terao N., Kuwahara M. Prognostic significance of cyclin E and p53 protein overexpression in carcinoma of the renal pelvis and ureter. Br J Cancer. 1998 Mar;77(5):783–788. doi: 10.1038/bjc.1998.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gabbert H. E., Müller W., Schneiders A., Meier S., Hommel G. The relationship of p53 expression to the prognosis of 418 patients with gastric carcinoma. Cancer. 1995 Sep 1;76(5):720–726. doi: 10.1002/1097-0142(19950901)76:5<720::aid-cncr2820760503>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  13. Gannon J. V., Greaves R., Iggo R., Lane D. P. Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form. EMBO J. 1990 May;9(5):1595–1602. doi: 10.1002/j.1460-2075.1990.tb08279.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Harris C. C., Hollstein M. Clinical implications of the p53 tumor-suppressor gene. N Engl J Med. 1993 Oct 28;329(18):1318–1327. doi: 10.1056/NEJM199310283291807. [DOI] [PubMed] [Google Scholar]
  15. Joypaul B. V., Hopwood D., Newman E. L., Qureshi S., Grant A., Ogston S. A., Lane D. P., Cuschieri A. The prognostic significance of the accumulation of p53 tumour-suppressor gene protein in gastric adenocarcinoma. Br J Cancer. 1994 May;69(5):943–946. doi: 10.1038/bjc.1994.182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kakeji Y., Korenaga D., Tsujitani S., Baba H., Anai H., Maehara Y., Sugimachi K. Gastric cancer with p53 overexpression has high potential for metastasising to lymph nodes. Br J Cancer. 1993 Mar;67(3):589–593. doi: 10.1038/bjc.1993.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kang S. M., Maeda K., Onoda N., Chung Y. S., Nakata B., Nishiguchi Y., Sowa M. Combined analysis of p53 and vascular endothelial growth factor expression in colorectal carcinoma for determination of tumor vascularity and liver metastasis. Int J Cancer. 1997 Oct 21;74(5):502–507. doi: 10.1002/(sici)1097-0215(19971021)74:5<502::aid-ijc4>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]
  18. Kim J. H., Takahashi T., Chiba I., Park J. G., Birrer M. J., Roh J. K., De Lee H., Kim J. P., Minna J. D., Gazdar A. F. Occurrence of p53 gene abnormalities in gastric carcinoma tumors and cell lines. J Natl Cancer Inst. 1991 Jul 3;83(13):938–943. doi: 10.1093/jnci/83.13.938. [DOI] [PubMed] [Google Scholar]
  19. Koechli O., Schaer G. N., Seifert B., Hornung R., Haller U., Eppenberger U., Mueller H. Mutant p53 protein associated with chemosensitivity in breast cancer specimens. Lancet. 1994 Dec 10;344(8937):1647–1648. doi: 10.1016/s0140-6736(94)90447-2. [DOI] [PubMed] [Google Scholar]
  20. Levine A. J., Momand J., Finlay C. A. The p53 tumour suppressor gene. Nature. 1991 Jun 6;351(6326):453–456. doi: 10.1038/351453a0. [DOI] [PubMed] [Google Scholar]
  21. Levine A. J., Perry M. E., Chang A., Silver A., Dittmer D., Wu M., Welsh D. The 1993 Walter Hubert Lecture: the role of the p53 tumour-suppressor gene in tumorigenesis. Br J Cancer. 1994 Mar;69(3):409–416. doi: 10.1038/bjc.1994.76. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Maehara Y., Okuyama T., Moriguchi S., Orita H., Kusumoto H., Korenaga D., Sugimachi K. Prophylactic lymph node dissection in patients with advanced gastric cancer promotes increased survival time. Cancer. 1992 Jul 15;70(2):392–395. doi: 10.1002/1097-0142(19920715)70:2<392::aid-cncr2820700204>3.0.co;2-p. [DOI] [PubMed] [Google Scholar]
  23. Maehara Y., Okuyama T., Oshiro T., Baba H., Anai H., Akazawa K., Sugimachi K. Early carcinoma of the stomach. Surg Gynecol Obstet. 1993 Dec;177(6):593–597. [PubMed] [Google Scholar]
  24. Maehara Y., Orita H., Okuyama T., Moriguchi S., Tsujitani S., Korenaga D., Sugimachi K. Predictors of lymph node metastasis in early gastric cancer. Br J Surg. 1992 Mar;79(3):245–247. doi: 10.1002/bjs.1800790320. [DOI] [PubMed] [Google Scholar]
  25. McLaren R., Kuzu I., Dunnill M., Harris A., Lane D., Gatter K. C. The relationship of p53 immunostaining to survival in carcinoma of the lung. Br J Cancer. 1992 Oct;66(4):735–738. doi: 10.1038/bjc.1992.348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Motojima K., Furui J., Kohara N., Ito T., Kanematsu T. Expression of p53 protein in gastric carcinomas is not independently prognostic. Surgery. 1994 Nov;116(5):890–895. [PubMed] [Google Scholar]
  27. Nakao A. An experimental study on the toxicity of 2,4,6-trichlorophenyl-4'-nitrophenyl ether (CNP) (author's transl). Fukuoka Igaku Zasshi. 1975 Feb;66(2):123–153. [PubMed] [Google Scholar]
  28. Narayana A., Vaughan A. T., Gunaratne S., Kathuria S., Walter S. A., Reddy S. P. Is p53 an independent prognostic factor in patients with laryngeal carcinoma? Cancer. 1998 Jan 15;82(2):286–291. doi: 10.1002/(sici)1097-0142(19980115)82:2<286::aid-cncr7>3.0.co;2-p. [DOI] [PubMed] [Google Scholar]
  29. Oiwa H., Maehara Y., Ohno S., Sakaguchi Y., Ichiyoshi Y., Sugimachi K. Growth pattern and p53 overexpression in patients with early gastric cancer. Cancer. 1995 Mar 15;75(6 Suppl):1454–1459. doi: 10.1002/1097-0142(19950315)75:6+<1454::aid-cncr2820751511>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  30. Porter P. L., Gown A. M., Kramp S. G., Coltrera M. D. Widespread p53 overexpression in human malignant tumors. An immunohistochemical study using methacarn-fixed, embedded tissue. Am J Pathol. 1992 Jan;140(1):145–153. [PMC free article] [PubMed] [Google Scholar]
  31. Quinlan D. C., Davidson A. G., Summers C. L., Warden H. E., Doshi H. M. Accumulation of p53 protein correlates with a poor prognosis in human lung cancer. Cancer Res. 1992 Sep 1;52(17):4828–4831. [PubMed] [Google Scholar]
  32. Sakaguchi T., Watanabe A., Sawada H., Yamada Y., Yamashita J., Matsuda M., Nakajima M., Miwa T., Hirao T., Nakano H. Prognostic value of cyclin E and p53 expression in gastric carcinoma. Cancer. 1998 Apr 1;82(7):1238–1243. doi: 10.1002/(sici)1097-0142(19980401)82:7<1238::aid-cncr5>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
  33. Starzynska T., Bromley M., Ghosh A., Stern P. L. Prognostic significance of p53 overexpression in gastric and colorectal carcinoma. Br J Cancer. 1992 Sep;66(3):558–562. doi: 10.1038/bjc.1992.314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sugimachi K., Maehara Y., Ogawa M., Kakegawa T., Tomita M. Dose intensity of uracil and tegafur in postoperative chemotherapy for patients with poorly differentiated gastric cancer. Cancer Chemother Pharmacol. 1997;40(3):233–238. doi: 10.1007/s002800050652. [DOI] [PubMed] [Google Scholar]
  35. Thor A. D., Moore DH I. I., Edgerton S. M., Kawasaki E. S., Reihsaus E., Lynch H. T., Marcus J. N., Schwartz L., Chen L. C., Mayall B. H. Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers. J Natl Cancer Inst. 1992 Jun 3;84(11):845–855. doi: 10.1093/jnci/84.11.845. [DOI] [PubMed] [Google Scholar]

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